Mycobacterium tuberculosis heat‐shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin‐10 production and inhibits T‐cell proliferation in vitro

Abstract

Summary In different inflammatory disease models, heat‐shock proteins (hsp) and hsp‐derived peptides have been demonstrated to possess anti‐inflammatory properties. While some studies have shown that hsp can directly interact with antigen‐presenting cells, others report that bacterial hsp can induce specific T cells with regulatory phenotypes. Effective characterization of the immunomodulatory effects of hsp 70, however, has historically been confounded by lipopolysaccharide (LPS) contamination. In this study, we compared the effects of LPS‐free Mycobacterial tuberculosis hsp 70 (TBhsp70) and its possible contaminants on dendritic cells (DC). We demonstrate herein that LPS‐free TBhsp70 inhibits murine DC maturation in vitro, while LPS‐contaminated TBhsp70 induces DC maturation. Mock recombinant preparations have no effect. In contrast to LPS, TBhsp70 does not induce tumour necrosis factor‐α production by DC, but interleukin‐10. In vivo, only LPS‐contaminated TBhsp70 induces up‐regulation of CD86 in splenic mature DC. Finally, TBhsp70 inhibited phytohaemagglutinin‐induced T‐cell proliferation. Our results support the hypothesis that TBhsp70 does not have inflammatory potential, but rather has immunosuppressive properties.

Inducible Heat Shock Protein 70 Reduces T Cell Responses and Stimulatory Capacity of Monocyte-derived Dendritic Cells

“…Consequently, we believe that our straightforward experimental setup provided true representation of Hsp70 function. In addition, our results are in agreement with the study by Motta et al where the PHA-induced proliferative response of murine splenocytes was down-regulated by endotoxin-free Mycobacterium tuberculosis Hsp70 (15).…”

“…The shared activation pathway as well as the similar activation profile for endotoxins and Hsp70 led to speculation that the observed cytokine-like property of Hsp70 may have been incorrectly identified. Accordingly, it was shown that the endotoxin contamination in recombinant Hsp70 is common and exclusively responsible for the described proinflammatory properties, including activation of APCs (12)(13)(14)(15)(16). It was also shown that endotoxin-free Hsp70 did not induce APC activation while still effectively delivered antigenic peptides for cross-presentation (17).…”

HspR Mutations Are Naturally Selected in Bifidobacterium longum When Successive Heat Shock Treatments Are Applied

“…Heat shock proteins are also known for their immunomodulator properties. In Mycobacterium tuberculosis, DnaK was reported for its immunosuppressive properties (22), which also suggests a new potential of our mutant strains for health-promoting applications.…”

Heat Shock Proteins in Mycobacterium tuberculosis: Involvement in Survival and Virulence of the Pathogen

“…Hsp70 induces the expression of IL-10 and inhibits T-cell proliferation in vitro. Hsp70 appears to have immunosuppressive properties rather than inflammatory potential (Motta et al, 2007).…”